Traumatic Stress and Alcohol Problems: Between- and Within- Person Associations

描述（由申请人提供）：本申请是对PA-10-255“酒精依赖的行为调节机制和相关表型”的回应，该申请旨在促进调节机制与酒精依赖、赋予酒精依赖风险的遗传和环境因素以及区分酒精依赖与相关外化行为的因素之间关系的研究。对伊拉克自由行动/持久自由行动退伍军人的拟议研究采用纵向突发设计来模拟创伤后应激障碍症状、酒精依赖和相关行为问题的动态过程。我们测试了关于潜在的调节缺陷、依赖与其他外化行为之间的分离以及基因与环境相互作用的假设。PTSD与酒精依赖以及导致社会和职业功能困难的相关外化问题有关（Frueh等人，2001；Hog等人，2007；Mills等人，2007；Seal等人，2011）。研究表明，影响行为调节的缺陷是连接创伤后应激障碍和酒精相关问题的两种不同途径（Miller et al., 2006）。我们认为这两种途径与不同类型的问题有关。最近关于物质依赖负强化模型的理论和研究强调了情感不稳定性在依赖发展中的作用，而不是消极情感的平均水平（Baker等人，2004；Simons等人，2009,2010b； Weinstein等人，2008）。创伤后应激障碍与明显的不稳定有关，我们认为正是这种情绪的变化给这一人群带来了酒精依赖的风险。相反，我们认为与PTSD和酒精使用相关的行为问题是行为去抑制的功能。去抑制作用介导PTSD与酒精问题之间的关联（Miller et al., 2006），而去抑制作用主要与酒精相关的行为问题而非依赖症状相关（Simons et al., 2009; 2010b）。虽然创伤暴露与PTSD和酒精问题的发展有关，但这些关联在不同的人之间存在显著的差异。我们假设5-羟色胺转运体相关多态性区域（5-HTTLPR）的基因型与创伤暴露相互作用，预测PTSD症状和酒精依赖，以及中间变量，影响不稳定性和行为去抑制。这项研究将检验监管机制的作用

DESCRIPTION (provided by applicant): This application is in response to PA-10-255 "Behavioral Regulation Mechanisms of Alcohol Dependence and Related Phenotypes", which seeks to promote research on associations between regulation mechanisms and alcohol dependence, genetic and environmental factors conferring risk for alcohol dependence, and factors differentiating alcohol dependence from related externalizing behaviors. The proposed study of Operation Iraqi Freedom / Operation Enduring Freedom veterans utilizes a longitudinal burst design to model the dynamic course of PTSD symptoms, alcohol dependence, and associated conduct problems. We test hypotheses regarding underlying regulatory deficits, dissociation between dependence and other externalizing behaviors, and gene x environment interactions. PTSD is related to alcohol dependence as well as associated externalizing problems resulting in difficulties in social and occupational functioning (Frueh, et al., 2001; Hog et al., 2007; Mills et al., 2007; Seal et al., 2011). Research indicates that deficits in affect an behavioral regulation are two distinct pathways linking PTSD and alcohol-related problems (Miller et al., 2006). We propose that these two pathways are associated with different types of problems. Recent theory and research on negative reinforcement models of substance dependence have highlighted the role of affect lability, rather than mean levels of negative affect, in the development of dependence (Baker et al., 2004; Simons et al., 2009, 2010b; Weinstein et al., 2008). PTSD is associated with marked lability, and we posit that it is this variability in mood that confers risk for the development of alcohol dependence in this population. In contrast, we propose that conduct problems associated with PTSD and alcohol use are a function of behavioral disinhibition. Disinhibition mediates associations between PTSD and alcohol problems (Miller et al., 2006) and disinhibition is primarily associated with alcohol-related conduct problems rather than dependence symptoms (Simons et al., 2009; 2010b). Although trauma exposure is associated with the development of PTSD and alcohol problems, there is significant variability in these associations across persons. We hypothesize genotype at the serotonin transporter linked polymorphic region (5-HTTLPR) interacts with trauma exposure to predict PTSD symptoms and alcohol dependence, as well as the intermediary variables, affect lability and behavioral disinhibition. The study will test the role of regulation mechanisms in growth of symptoms over time, acute changes in the outcomes via person x situation effects, and test reciprocal effects of alcohol consumption on lability and PTSD symptoms. By integrating assessment of genetic and environmental risk, basic behavioral regulation deficits, and alcohol dependence and related conditions the study can improve our understanding of etiology, risk and resilience mechanisms, and potential mechanisms of therapeutic change.